Mapping of complex traits to gather information pertaining to genetic human disorders is seeing a tremendous and exciting era. Researchers everywhere have surfaced with novel designs, linkage and association methods to aid in the identification of the genes responsible for these diseases. However, success in such research has been largely restricted to simple, rare Mendelian diseases. The broad expanse of common and complex human disorders remains uncharted territory, despite past attempts for deriving information from such realms. In this proposal we offer a possible resolution to this problem. Our long term objective is to develop a novel and applicable method for breaking the barriers set between the limited ground of Mendelian diseases and important findings to common and complex diseases.
Specific aims i nclude: 1) Providing a new and realistically applicable method to address the important problems posed in the mapping of complex traits. The proposed method embodies two-stages: a) selecting a subset of markers that contain important susceptibility information regarding the traits under study and b) carrying out a detailed analysis and network construction on the selected markers, by clustering markers through evaluation of the interactive effects from the markers on the traits of interests. 2) Procuring a method appropriate and powerful for the variety of study designs and data types implemented by the scientific community. We propose to study a limited number of extensions in depth, which would accommodate researchers who conduct studies on human genetic disorders in their own study designs and data forms. 3) Developing user-friendly computational packages and tools based on the algorithm proposed for convenient usage of our methods in current and future genetic mapping of complex diseases. This project amounts to great importance in the convenience and overall accessibility of our proposed algorithm to present and future scientists. The proposed aims intend to remove the barriers current researchers face in approaching non-Mendelian diseases for information, provide routine guidelines for future investigators, and promote the quality of public welfare.
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